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Hema Diagnostic Test Awaits Results of African Trials, Could Rule Out TB for Less Than $2

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NEW YORK (360Dx) – If field trials prove successful, a point-of-care diagnostic test for tuberculosis could be available for less than $2 in resource-limited countries.

The test's developer, Hema Diagnostic Systems, a subsidiary of Generex Biotechnology, further noted that the test can get results in 15 minutes from a single drop of blood.

If the trials show that the antigen-based lateral flow test has the required levels of sensitivity and specificity, it could be used as a primary triage assay along with other tests, such as molecular diagnostic assays, to inform clinicians in the difficult process of diagnosing TB, Hema Diagnostics CEO Harold Haines said in an interview.

It could prove to be particularly adept as a rule-out test, he added.

"If clinicians are 90 to 95 percent certain that a patient does not have TB, then they can focus resources on people that have it," Haines said. Patients that are unlikely to have tuberculosis can be saved from the expense of unneeded tests such as chest X-rays and laboratory-based solutions, Haines added.

"TB is an economic problem as much as it is a diagnostic problem, because many countries don't have the money to pay for costly tests," Haines said.

A series of planned trials for the test, which are being conducted as part of a long-term project for the control of HIV and related diseases in some sub-Saharan African countries, has been initiated by the Community of Sant’Egidio, an Italian non-governmental organization. The trials are being sponsored by the Italian National Institute of Health. The University of Rome Tor Vergata is managing the clinical trial, and Fondazione Salvatore Maugeri, a center for tuberculosis and lung diseases in Tradate, Italy, is also participating.

The ultimate objective of the series of trials is to determine the accuracy and clinical validity of the Hema Diagnostic Systems rapid test. Haines noted that the commercial potential of the TB test depends largely on the results of a trial just completed in Mozambique, for which the firm is awaiting results, as well as how it fares in a series of planned subsequent trials in Africa, Peru, and Mexico. He said that he believes, based on validation trials internal to Hema Diagnostic, that the test will demonstrate that it has levels of sensitivity and specificity high enough that it can be used to rule out TB at the point of care.

Nathifa Bradshaw, director of regulatory affairs at Hema Diagnostic Systems, said in an interview that she believes the POC test will be CE marked within five months.

In parallel with participating in field trials that enable collecting test data in trials to further validate the test, the company also has plans to apply for clearance with the US Food and Drug Administration. The firm has no expectations around a timeline to receive FDA clearance, Haines said, but it does expect that an FDA clearance or CE mark will set the stage for deploying the test in resource-challenged settings and broadening access to TB testing where it is most needed.

People ask "why it is important to get FDA clearance, because the prevalence of TB is relatively low in the US, and the commercial opportunity [in the US] is also low," Haines said. "We want to have it validated in the US because the FDA has a degree of authority that we would like to leverage," he said. Having a CE mark and FDA clearance might not even be needed to obtain registrations in countries with high levels of prevalence, Haines said, but it would give greater credence to its commercial initiatives. After receiving required registrations, the firm plans to work with entities such as the World Health Organization and other suitable organizations "so that we can have the test inserted in countries that have a high prevalence of TB."

Hema Diagnostic Systems developed its Express test platform that runs the TB test after licensing proprietary antibodies and strips from Lionex, a Braunschweig, Germany-based biotech.

In operation, serum or plasma from a blood drop runs along a test strip that contains a mix of TB antigens. If TB antibodies are present in the sample, they adhere to the antigens and their presence can be observed by the development of a visible colored line.   

There are two versions of the test, the TB-XT and the TB-XT3, and Lionex provides test strips and antigen mixes for both versions under a licensing agreement with Hema Diagnostic. The TB-XT3 is a more advanced version of the TB-XT, Haines said, because it uses a second line that consists of an antigen that "significantly improves the sensitivity and specificity of the original test."

Internal evaluations have demonstrated that the assay has sensitivities and specificities high enough to operate the test in the field as part of a combination test approach, he noted, though he declined to share the sensitivity and specificity values as they have not yet been published in a peer-reviewed journal.

In the Mozambique trial, 300 archived samples, for which patients' clinical data was available, were used, Haines said. Future trials will include new patient samples.

Depending on the results, the lateral flow test would probably be most often used to diagnose at-risk groups identified as having high prevalence, Haines said. It will be used to test people who have symptoms, night sweats, fevers, and coughing, or who have had contact with people in the family who have TB, as well as anything else that might lead the physician to think that the patient could have TB.

Just as importantly, the test would be used to rule out patients who don't have TB, and prevent them from further unnecessary testing. If confirmation of TB is required, a test such as Cepheid's GeneXpert TB, could be used. The molecular assay can provide results in as little as two hours, Haines said.

That combination would be far better than the gold standard for diagnosing TB, which is a culture test, which can provide a definitive positive diagnosis, but can take four to eight weeks for test results, he said.

That, along with the investment required to conduct culture-based testing can limit the number of patients that are tested, he noted. Many patients in resource-limited countries cannot be reached for follow-up because of the delay in receiving culture-based results, he said.

With lost time, "you can't treat the patient in an expeditious manner," and they could die, he said. The sensitivity of a culture test can also be low, because not all people who have TB provide a positive result from a culture.

Joseph Moscato, president and CEO of Generex Biotechnology, noted that in African towns, the current approach for diagnosing and treating people suspected of carrying the TB infection is to have people travel to a central location, usually a town, and present for a blood draw.

With the Hema Diagnostic test, if 300 people present for testing, you may, hypothetically, be able to rule out 200 of them, he said, and the remaining people would then receive standard testing. The cost saving of not having to send all 300 cassettes to a laboratory are "dramatic," Moscato said.

Additionally, the lateral flow test could be transported to people in populations that have high prevalence of TB, so clinicians are not relying on people showing up for testing, he said.

Tuberculosis is an age-old scourge and continues to be a major cause of morbidity and mortality worldwide. Citing WHO estimates, Hema Diagnostic said there were 10.8 million new cases of TB in 2015, 1.4 million deaths in the non-HIV population, and 390,000 deaths in patients infected with HIV.

"Our hope [for the TB test] is that we can get up to 85 percent specificity and sensitivity," Moscato said. "We also hope that the results of the trial in Mozambique will be available sometime before our annual meeting in November."

Moscato noted that the company is investigating areas other than TB for use of its platform. One potential application is for the detection of the Zika virus, and the company expects to soon file a 510(k) application with the FDA so that it can receive clearance to market a test for syphilis, he noted.